title: Overexpressed cyclophilin B suppresses apoptosis associated with ROS and Ca2+ homeostasis after ER stress.
abstract: Prolonged accumulation of misfolded proteins in the endoplasmic reticulum (ER) results in ER stress-mediated apoptosis. Cyclophilins are protein chaperones that accelerate the rate of protein folding through their peptidyl-prolyl cis-trans isomerase (PPIase) activity. In this study, we demonstrated that ER stress activates the expression of the ER-localized cyclophilin B (CypB) gene through a novel ER stress response element. Overexpression of wild-type CypB attenuated ER stress-induced cell death, whereas overexpression of an isomerase activity-defective mutant, CypB/R62A, not only increased Ca(2+) leakage from the ER and ROS generation, but also decreased mitochondrial membrane potential, resulting in cell death following exposure to ER stress-inducing agents. siRNA-mediated inhibition of CypB expression rendered cells more vulnerable to ER stress. Finally, CypB interacted with the ER stress-related chaperones, Bip and Grp94. Taken together, we concluded that CypB performs a crucial function in protecting cells against ER stress via its PPIase activity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species, BK-21, School of Medicine, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Kim
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Choi
authors.forename: Yan
authors.initials: Y
authors.lastname: Ding
authors.forename: Yeonghwan
authors.initials: Y
authors.lastname: Kim
authors.forename: Kwon Soo
authors.initials: KS
authors.lastname: Ha
authors.forename: Kyung Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Randal J
authors.initials: RJ
authors.lastname: Kaufman
authors.forename: Jinhwa
authors.initials: J
authors.lastname: Lee
authors.forename: Wonchae
authors.initials: W
authors.lastname: Choe
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D021983:Cyclophilins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005786:Gene Expression Regulation; D006706:Homeostasis; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D051381:Rats; D017382:Reactive Oxygen Species; D014158:Transcription, Genetic
chemical_list: D017382:Reactive Oxygen Species; C081786:cyclophilin B; D021983:Cyclophilins; D002118:Calcium